Proliferative Diabetic Retinopathy Subjects Research Articles

Comparative proteomics of proliferative diabetic retinopathy in people with Type 2 diabetes highlights the role of inflammation, visual transduction, and extracellular matrix pathways.

To explore the vitreous humor proteome from type 2 diabetes subjects with proliferative diabetic retinopathy (PDR) in the Indian population. We performed mass spectrometry-based label-free quantitative analysis of vitreous proteome of PDR (n = 13) and idiopathic macular hole (IMH; control) subjects (n = 14). Nine samples of PDR and 10 samples of IMH were pooled as case and control, respectively, and compared. Four samples each of PDR and IMH were analyzed individually without pooling to validate the results of the pooled analysis. Comparative quantification was performed using Scaffold software which calculated the fold changes of differential expression. Bioinformatics analysis was performed using DAVID and STRING software. We identified 469 proteins in PDR and 517 proteins in IMH vitreous, with an overlap of 172 proteins. Also, 297 unique proteins were identified in PDR and 345 in IMH. In PDR vitreous, 37 proteins were upregulated (P < 0.05) and 19 proteins were downregulated compared to IMH. Protein distribution analysis clearly demonstrated a separation of protein expression in PDR and IMH. Significantly upregulated proteins included fibrinogen gamma chain, fibrinogen beta chain, and carbonic anhydrase 1 and downregulated proteins included alpha-1-antitrypsin, retinol-binding protein 3, neuroserpin, cystatin C, carboxypeptidase E and cathepsin-D. Diabetic retinopathy pathogenesis involves proteins which belong to inflammation, visual transduction, and extracellular matrix pathways. Validation-based experiments using enzyme-linked immunosorbent assay (ELISA) or western blotting are needed to establish cause and effect relationships of these proteins to the disease state, to develop them as biomarkers or drug molecules.

Internal Limiting Membrane Peeling in Patients Undergoing Vitrectomy for Tractional Retinal Detachment Secondary to Diabetic Retionpathy.

To assess the merits of internal limiting membrane (ILM) peeling during pars plana vitrectomy (PPV) in subjects with a tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy (PDR). One hundred and ninety one PDR subjects undergoing PPV for the principal indication of TRD were enrolled into this randomized controlled trial. Study subjects were intraoperatively randomized into one of the following treatment groups: Cohort A patients underwent ILM peeling, while Cohort B patients did not undergo ILM peeling. The main outcome was postsurgical epiretinal membrane (ERM) development at 6 months. The secondary outcome was attainment of ≥ 20/50 visual acuity (Snellen) at 6 months. One hundred and thirty nine subjects underwent randomization and completed the study's 6-month trial period. Cohort A had 3.1% (2/64) of subjects develop an ERM postoperatively, while Group B had 26.7% (20/75) of subjects develop an ERM postoperatively at 6 months (p<0.001). Attainment of ≥ 20/50 visual acuity (Snellen) at 6 months was found in 21.9% (14/64) of subjects in Cohort A and 9.3% (7/75) of subjects in Cohort B (p=0.039). PDR patients undergoing PPV for TRD have a lower frequency of postsurgical ERM formation and a greater likelihood of attaining ≥ 20/50 Snellen visual acuity at 6 months when ILM peeling is conducted. Specialists may consider peeling of the ILM during PPV an important surgical maneuver in this patient population.

Gas Tamponade for the Prevention of Postoperative Vitreous Hemorrhaging After Diabetic Vitrectomy: A Randomized Clinical Trial

To compare vitreous substitution with sulfur hexafluoride (SF6) gas to balanced salt solution (BSS) for the prevention of postoperative vitreous hemorrhage (VH) in proliferative diabetic retinopathy (PDR) patients undergoing pars plana vitrectomy (PPV) for the indication of non-clearing VH. One hundred forty-four PDR subjects requiring PPV for the indication of non-clearing VH were enrolled into the trial. Subjects were prospectively randomized into 1 of 2 vitreous substitution groups: Group A subjects underwent 20% to 30% SF6 gas tamponade, whereas Group B subjects underwent vitreous substitution with BSS. The primary outcome was the incidence of postoperative VH during the 6-month trial period. Secondary outcomes were unplanned PPV for VH and best corrected visual acuity (BCVA) at 6-months follow-up. Ninety-six subjects underwent randomization and completed 6-months follow-up. Postoperative VH during the trial period occurred in 6 of 54 subjects in Group A (SF6) (11.1%) and 14 of 42 in Group B (BSS) (33.3%) (P=.008). Unplanned PPV during the trial period for postoperative VH occurred in 2 of 54 in Group A (3.7%) and 6 of 42 in Group B (14.2%) (P=.06). The mean BCVA was not significantly different at 6-months follow-up between groups (P=.58). This trial indicates that vitreous substitution with SF6 gas lowers the incidence of postoperative VH compared with BSS in PDR subjects undergoing PPV for the indication of non-clearing VH at 6-months follow-up. Specialists may consider SF6 gas tamponade during PPV as a means of helping reduce postoperative VH in this patient population. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

The retinal nerve fiber layer thickness is useful for the assessment of diabetic retinopathy severity

ObjectiveTo assess the alterations of individual retinal layer thickness at different stages of diabetic retinopathy (DR) and its role in determining DR severity. MethodsIn this study, 51 patients with nonproliferative DR (NPDR) and 57 patients with proliferative DR (PDR) were enrolled. The individual retinal layer thickness was measured according to the image segmentation of the macular scan collected from the optical coherence tomography (OCT) result. Comparative analysis was performed in addition to assessment of the diagnostic performance of the retina layer using receiver-operating-curve (ROC) analysis. Moreover, correlation analysis was conducted to examine the association between HbA1c and retina layer changes. ResultsIn PDR subjects, the retinal nerve fiber layer (RNFL, p < 0.0001), ganglion cell layer (GCL, p < 0.0001), inner plexiform layer (IPL, p = 0.0025), ganglion cell-inner plexiform layer (GC-IPL, p < 0.0001), and ganglion cell complex (GCC = RNFL+GCL+IPL, p < 0.0001) thickness were decreased compared to NPDR subjects. RNFL exhibited a better performance than GCL, GC-IPL, or GCC (AUC for RNFL = 0.76, p < 0.0001) in discriminating DR severity (cut-off of 16.62 μm (84.21% sensitivity and 70.59% specificity). The RNFL, GCL, IPL, GC-IPL, GCC, inner nuclear layer (INL), and total retinal layer (TLR) thickness correlated negatively with HbA1c levels in PDR group. ConclusionMeasurement of retinal degeneration, particularly by evaluating RNFL thinning is potentially useful for early identification of DR progression.

Altered oxylipin levels in human vitreous indicate imbalance in pro-/anti-inflammatory homeostasis in proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) is an advanced stage of diabetic retinopathy (DR), characterized by retinal neovascularization. It is a progressive fundus disease and a severe complication of diabetes that causes vision impairment. Hyperglycemia-induced persistent low-grade inflammation is a crucial factor underlying the pathogenesis of DR-associated damage and contributing to the progression of PDR. Highly enriched polyunsaturated fatty acids (PUFAs) in the retina are precursors to oxidized metabolites, namely, oxylipins, which exert pro-inflammatory or anti-inflammatory (resolving) effects under different pathological conditions and have been implicated in diabetes. To evaluate differences in oxylipin levels in the vitreous obtained from PDR and non-diabetic subjects, we performed a targeted assessment of oxylipins. A total of 41 patients with PDR and 22 non-diabetic control subjects were enrolled in this study. Vitreous humor obtained during routinely scheduled vitrectomy underwent a targeted but unbiased screening for oxylipins using mass spectrometry-based lipidomics. We found 21 oxylipins showing statistically significant differences in their levels between PDR and non-diabetic subjects (p < 0.05). Lipoxygenase (LOX)- and cytochrome P450 (CYP)- derived oxylipins were the most affected, while cyclooxygenase (COX) oxylipins were affected to a lesser extent. When categorized by their precursor PUFAs, ±19,20-EpDPE, a CYP product of docosahexaenoic acid (DHA) and 12S-HETE, a LOX product of arachidonic acid (ARA), were increased by the largest magnitude. Moreover, of these 21 oxylipins, 7 were considered as potential biomarkers for discriminating PDR patients from the non-diabetic controls. Our results indicate that altered oxylipin levels in the vitreous implicate an underlying imbalanced inflammation-resolution homeostasis in PDR.

Could Vitamin D be Associated with Proliferative Diabetic Retinopathy? Evidence from Pooling Studies

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

Upregulation of Lysyl Oxidase Expression in Vitreous of Diabetic Subjects: Implications for Diabetic Retinopathy.

Animal studies have shown diabetes-induced lysyl oxidase (LOX) upregulation promotes blood-retinal-barrier breakdown and retinal vascular cell loss associated with diabetic retinopathy (DR). However, it is unclear whether changes in LOX expression contribute to the development and progression of DR. To determine if vitreous LOX levels are altered in patients with DR, 31 vitreous specimens from subjects with advanced proliferative DR (PDR), and 27 from non-diabetics were examined. The two groups were age- and gender-matched (57 ± 12 yrs vs. 53 ± 18 yrs; 19 males and 12 females vs. 17 males and 10 females). Vitreous samples obtained during vitrectomy were assessed for LOX levels using ELISA. LOX was detected in a larger number of PDR subjects (58%) than in non-diabetic subjects (15%). Additionally, ELISA measurements showed a significant increase in LOX levels in the diabetic subjects with PDR, compared to those of non-diabetic subjects (68.3 ± 112 ng/mL vs. 2.1 ± 8.2 ng/mL; p < 0.01). No gender difference in vitreous LOX levels was observed in either the diabetic or non-diabetic groups. Findings support previous reports of increased LOX levels in retinas of diabetic animals and in retinal vascular cells in high glucose condition, raising the prospect of targeting LOX overexpression as a potential target for PDR treatment.

Polimorfisme V16A Gen MnSOD pada Penderita Diabetes Melitus Tipe 2 dengan Retinopati

Complications of diabetes mellitus (DM) include diabetic retinopathy (RD) both non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). The development of RD depends on environmental and genetic factors. MnSOD gene (manganese-superoxid dismutase) is one of the candidate risk factors gene for RD. The presence of V16A MnSOD gene polymorphism results in decrease of mitochondrial MnSOD enzymes expression and triggers the oxidative stress. Hyperglycemia in DM increases oxidative stress in tissues, including the retina resulting in metabolic abnormalities in the retina, which play a role in the development of DM complications, namely diabetic retinopathy. In Indonesia, especially the Javanese tribes in Yogyakarta, there has never been any research on MnSOD gene polymorphism in type 2 diabetes patients with and without retinopathy. Subjects were Poly Endocrine patients and Eye Polyclinic patients of Dr. Sardjito’s General Hospital, 121 subjects consisting of 63 type 2 DM patients without retinopathy were group 1 (KI) and 58 type 2 DM patients with retinopathy were group 2 (KII) (20 NPDR subjects and 38 PDR subjects). V16A polymorphism of MnSOD gene from leukocytes DNA was analyzed by PCR-RFLP method. From 121 DM subjects, 70 subjects with VV genotype were found, 50 subjects with VA genotype and 1 subject with AA genotype. From 63 non-RD DM subjects, 22 subjects with VA genotypes and 41 subjects with VV genotype were found, while in DM with retinopathy (non-PDR, n = 20) found 6 subjects with VA genotype and 14 subjects with VV genotype, and in DM with retinopathy (PDR, n = 38) found 1 subject with AA genotype, 22 subjects with VA genotype and 15 subjects with VV genotype. In DM with retinopathy (NPDR and PDR, n = 58), 1 subject was found with AA genotype, 27 subjects with VA genotype and 29 subjects with VV genotype.

Quantitative proteomics analysis of vitreous body from type 2 diabetic patients with proliferative diabetic retinopathy

BackgroundTo compare the abundance of vitreous proteins between the patients with proliferative diabetic retinopathy (PDR) and idiopathic macular hole (IMH).MethodsIn this study, we performed mass spectrometry-based label-free quantitative proteomics analysis of vitreous samples from type 2 diabetic patients with PDR (n = 9) and IMH subjects (n = 9) and identified the abundance of 610 proteins.ResultsOut of 610 proteins, 64 proteins (Group A) were unique to PDR patients, while 212 proteins (Group B) could be identified in IMH vitreous only. Among the other 334 proteins that could be detected in both PDR and IMH eyes, 62 proteins differed significantly (p < 0.05, fold change > 2), which included 52 proteins (Group C) and 10 proteins (Group D) over- and under-expressed in PDR vitreous compared with the control. All proteins in these four groups were counted as significant proteins in our study.ConclusionsWe identified and quantified 610 proteins in total, which included 338 significant proteins in our study. Protein distribution analysis demonstrated a clear separation of protein expression in PDR and IMH. The protein function analysis illustrated that immunity and transport related proteins might be associated with PDR.

Serum Extracellular Superoxide Dismutase Is Associated with Diabetic Retinopathy Stage in Chinese Patients with Type 2 Diabetes Mellitus.

Extracellular superoxide dismutase (ecSOD) is the major extracellular scavenger of reactive oxygen species and associated with the diabetic complication in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the serum ecSOD activity in Chinese patients with different stages of diabetic retinopathy (DR) and evaluate the association between the serum ecSOD activity and the severity of DR. A total of 343 T2DM patients were categorized into three groups: nondiabetic retinopathy (NDR) group, nonproliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Serum ecSOD activities were measured by the autoxidation of the pyrogallol method. In this study, 271, 46, and 26 patients were enrolled in the NDR, NPDR, and PDR groups, respectively. We found a significantly decreased trend of serum ecSOD activity among NDR subjects (118.0 ± 11.5 U/mL) compared to NPDR subjects (108.5 ± 11.9 U/mL) (P < 0.001) and NPDR subjects compared to PDR subjects (102.7 ± 12.4 U/mL) (P = 0.041). Serum ecSOD activity was an independent risk factor for DR (OR = 0.920, P < 0.001) and was associated with the progression of DR. Serum ecSOD activity might be a biomarker for DR screening and evaluation of the clinical severity of DR in Chinese T2DM patients.

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy.

(Pro)renin receptor [(P)RR], a new component of the tissue renin-angiotensin system (RAS), plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR). In this study, we investigated systemic factors related to plasma levels of soluble form of (P)RR [s(P)RR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(P)RR, prorenin, tumor necrosis factor (TNF)-α, complement factor D (CFD), and leucine-rich α-2-glycoprotein 1 (LRG1) significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(P)RR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(P)RR, but not prorenin, levels. Among the inflammatory molecules correlated with s(P)RR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (P)RR but not prorenin, while stimulation with high glucose enhanced both (P)RR and prorenin expression. These findings suggested close relationships between plasma s(P)RR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.

Characterization of Vitreous and Aqueous Proteome in Humans With Proliferative Diabetic Retinopathy and Its Clinical Correlation.

Aims:Proliferative diabetic retinopathy (PDR) is associated with microvascular complications that cause biochemical changes in the human retina and alter the proteome of vitreous humor and aqueous humor (AH).Methods:Human vitreous humor and AH of PDR subjects were collected. Subjects who had surgery for epiretinal membrane or macular hole served as controls. Protein profiles were obtained and analyzed after running the samples on a liquid chromatography-mass spectrometry/mass spectrometry.Results:In vitreous humor, 16 unique proteins were noted in PDR patients, but not in controls. Those were associated mainly with coagulation, complement, and kallikrein-kinin systems. Under coagulation, fibrinogen and prothrombin proteins were more evident and may emphasize the importance of angiogenesis in the development of PDR. Vitreous proteins showed replicative presence in AH too. As for AH samples, we detected 10 proteins found in PDR patients, which were related to transport, coagulation, and inflammatory responses.Conclusions:We found 57 proteins in human vitreous and 39 proteins in AH. Identification of these proteins that are involved in various pathways will be helpful to understand diabetic retinopathy pathogenesis and to develop proteome as a biomarker for PDR.

Myeloid-Related Protein-14/MRP-14/S100A9/Calgranulin B is Associated with Inflammation in Proliferative Diabetic Retinopathy

ABSTRACTPurpose: To investigate the expression of the leukocyte proteins myeloid-related protein (MRP)-8 and MRP-14 in proliferative diabetic retinopathy (PDR) and the effect of MRP-8/MRP-14 (calprotectin) heterodimer on induction of proinflammatory factors in human retinal microvascular endothelial cells (HRMEC).Methods: Epiretinal membranes from 20 patients with PDR and 10 patients with proliferative vitreoretinopathy (PVR), vitreous fluid samples from PDR and non-diabetic subjects and HRMEC were studied by immunohistochemistry and Western blot analysis.Results: MRP-14 expression was localized in endothelial cells, leukocytes and myofibroblasts in all PDR membranes. MRP-8 expression was limited to intravascular leukocytes in 42% of the studied membranes. In PVR membranes, MRP-14 was expressed in leukocytes and myofibroblasts, whereas MRP-8 immunoreactivity was limited to leukocytes. MRP-14 was significantly upregulated in vitreous from PDR patients. MRP-8/MRP-14 (calprotectin) increased expression of intercellular adhesion molecule-1, but attenuated vascular cell adhesion molecule-1 expression in HRMEC.Conclusions: Increased MRP-14 levels are associated with inflammation in PDR.

Telomere mean length in patients with diabetic retinopathy.

Telomere regression has been shown to be associated with several complex disorders like diabetes mellitus, cancer, cataract etc. Diabetic retinopathy develops as a complication of chronic hyperglycemia leading to increased oxidative stress that may potentially lead to shortening of telomeres. We sought to determine whether there is any association between telomere mean length (TML) of peripheral blood monocytes with the presence and severity of diabetic retinopathy. The study involved 120 subjects, comprising 27 non-insulin dependent diabetes mellitus (NIDDM) without any diabetic retinopathy (NDR), 45 NIDDM subjects with non-proliferative diabetic retinopathy (NPDR), 12 NIDDM subjects with proliferative diabetic retinopathy (PDR) and 36 healthy controls. Determination of TML of the study subjects was performed by Southern hybridization using telomere probe. Among the biochemical parameters, HBA1c showed a negative correlation with shortened telomeres in the PDR subjects. However, telomere length was positively correlated with high density lipo protein (HDL) in the control subjects. The control group had significantly greater TML as compared to the rest of the groups and the NDR subjects with NPDR and PDR had substantially decreased TML than the NIDDM subjects without retinopathy.

Role of NF-κB activation and VEGF gene polymorphisms in VEGF up regulation in non-proliferative and proliferative diabetic retinopathy.

The present study was aimed to investigate the relation between nuclear factor kappa beta (NFκB) activation and downstream up-regulation of vascular endothelial growth factor (VEGF) in diabetic retinopathy (DR). Moreover the study was intended to evaluate the role of VEGF gene single nucleotide polymorphisms (SNPs) in DR occurrence and to investigate the functional relevance of VEGF gene SNPs in terms of VEGF expression in DR. Serum level of VEGF, VEGF R1 (receptor 1), VEGF R 2 (receptor 2) and NFκB (p50/65) activity was measured by enzyme linked immune sorbent assay. Genotyping and allelic composition of different SNPs i.e., rs2010963, rs3025039, rs1570360 and rs 2071559 were investigated by Taqman SNP genotyping assay. VEGF, NFκB p50/p65, and VEGF R1 & R2 gene expressions were quantified by real time quantitative polymerase chain reaction. Increased NFκB p50/p65 activity and expressions were observed in non proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) subjects compared to type 2 diabetes mellitus without retinopathy (DNR) group. Significantly elevated levels of serum VEGF and highest VEGF expression were found among PDR subjects compared to DNR or NPDR subjects. CC genotype and C allele of rs2010963 and TT genotype and T allele of rs3025039 were significantly over represented among PDR subjects compared to DNR group. Increased activation of NFκβ in NPDR and PDR subjects might involve increased up regulation of VEGF. VEGF SNPs i.e., rs2010963 C allele and rs3025039 T allele might be associated with PDR occurrence and in turn regulates VEGF expression among PDR subjects.

Neural Constraints on Visual Acuity in Proliferative Diabetic Retinopathy

Visual acuity (VA) in normally sighted individuals is highly correlated with equivalent intrinsic blur, a measure of the amount of blur within the visual system that is generated by optical and neural sources. This study assessed the extent to which VA, equivalent intrinsic blur, optical blur, and neural blur are abnormal in subjects with proliferative diabetic retinopathy (PDR) and characterized the relationships among these parameters. Best-corrected VA of 10 subjects with PDR (ages 25 to 68) and 10 normally sighted individuals (ages 46 to 63) was measured for tumbling E optotypes. The Es were either unblurred or blurred through convolution with Gaussian functions of different widths. Values of equivalent intrinsic blur (σ(int)) and unblurred VA (MAR0) were derived using a standard model. Optical blur (σ(opt)), a measure of blur generated by higher-order aberrations, was quantified using Shack-Hartmann aberrometry. An index of neural blur (η) was defined as 1--σ(opt)/σ(int), which represents the remaining blur once the contributions of σ(opt) to σ(int) have been accounted for. Log MAR0 and log σ(int) were correlated significantly (r = 0.98, p < 0.05) for the PDR subjects and the values of these parameters ranged from normal to more than a factor of 2 above the upper limit of normal. In comparison, log MAR measured for the most blurred E was elevated by a relatively small amount for all PDR subjects and was not correlated significantly with log σ(int) (r = 0.40, p = 0.25). MAR0, σ(int), and η differed significantly between the PDR subjects and the controls (all p < 0.05) but σ(opt) did not (p = 0.50). Subjects with PDR and VA loss had higher than normal equivalent intrinsic blur that resulted primarily from neural blur elevations, suggesting that neural blur is an important factor that limits VA in these patients.

Association of hyperglycemia mediated increased advanced glycation and erythrocyte antioxidant enzyme activity in different stages of diabetic retinopathy

AimThis study aimed to evaluate whether hyperglycemia mediated increased formation of advanced glycation end products (AGEs) was associated with erythrocyte antioxidant enzyme activity in subjects with different stages of diabetic retinopathy (DR). MethodsSerum level of AGEs was determined by enzyme linked immunosorbent assay. Erythrocyte superoxide dismutase (SOD), glutathione reductase (GR) and catalase activity were estimated by enzymatic reaction based spectrophotometric assay in patients with type 2 diabetes with proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR) and no retinopathy (DNR) and also in healthy non-diabetic controls (HC). ResultErythrocyte SOD and GR activity was significantly lower among NPDR (p=0.024, 0.0017, respectively) and PDR (p=0.0003, 0.0001, respectively) subjects compared with DNR individuals. A significant inverse correlation was observed between serum AGEs and erythrocyte SOD or GR activity in DNR (p=0.0019; r=−0.3033, p=0.0021; r=−0.3015, respectively), NPDR (p=0.0001; r=−0.4602, p=0.0003; r=−0.4161, respectively), and PDR (p<0.0001; r=−0.6753, p<0.0001; r=−0.5854, respectively) individuals. ConclusionPoor glycemia may be the key factor enhancing AGE formation, which may be associated with lower erythrocyte SOD and GR activity along with increased catalase activity in DR.

Retinal Vascular Calibre, Geometry and Progression of Diabetic Retinopathy in Type 2 Diabetes Mellitus

Purpose: To determine whether changes in retinal vascular calibre and geometry are associated with progression of diabetic retinopathy in type 2 diabetes (T2D). Procedures: The retinal vascular calibre and geometry of 30 subjects with more than 20 years of diagnosed T2D with no retinopathy (NR) were compared to 30 subjects that progressed to proliferative diabetic retinopathy (PDR). The images of PDR subjects included in this study were those obtained before the onset of retinopathy. The diameter of retinal arterioles (CRAE), retinal venules (CRVE), tortuosity of retinal vessels, junctional exponent deviation (JE_a) and fractal dimension (D_f) were measured using Singapore I Vessel Assessment (SIVA 3.0) software and compared using Mann-Whitney U test. Results: The median CRAE and the median CRVE were significantly wider in PDR subjects compared to NR subjects (p = 0.014 and 0.016), respectively. Curvature tortuosity of the retinal arteries and veins and D_f were significantly decreased in the PDR subjects compared to NR subjects (p = 0.015, 0.016 and 0.03, respectively). The JE_a was significantly increased in PDR subjects (p = 0.01). Conclusions: Retinal vessel calibre and geometry of the retinal vasculature may be important risk factors for the progression to PDR. More longitudinal prospective studies will be needed to further explore the findings of this study.

Low serum apolipoprotein A1/B ratio is associated with proliferative diabetic retinopathy in type 2 diabetes

The association between lipids and diabetic retinopathy (DR) remains unclear. Only a few studies have reported the association between proliferative diabetic retinopathy (PDR) and the serum concentrations of apolipoprotein A1 (apoA1), apolipoprotein B (apoB) and apolipoprotein E (apoE). So we investigated the lipid profile in type 2 diabetic patients of long duration with very mild nonproliferative diabetic retinopathy (NPDR) or PDR. Serum samples were obtained from 25 type 2 diabetic patients with very mild NPDR and 25 type 2 diabetic patients with PDR, and the two groups were matched by diabetes duration and glycosylated hemoglobin (HbA(1c)) levels. The levels of total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, apoA1, apoB, and apoE were measured by enzymatic colorimetric, surfactant, and immunotubidimetric method. Compared with PDR subjects, very mild NPDR subjects were characterized by increased HDL cholesterol (P = 0.0433) and apoA1 (P = 0.0290) levels, higher HDL cholesterol/LDL cholesterol (P = 0.0377) and apoA1/apoB (P = 0.0061) ratio in serum. There were significant associations between the decreased apoA1 and low apoA1/apoB ratio in serum and PDR. Even after adjustment for age, decreased apoA1 level (P = 0.0304) and low apoA1/apoB ratio (P = 0.0218) in serum were significantly associated with PDR in type 2 diabetic patients of over 15years' duration. Low apolipoprotein A1/apolipoprotein B ratio in serum was associated with PDR in type 2 diabetic patients of long duration.

Association between Subclinical Hypothyroidism and Proliferative Diabetic Retinopathy in Type 2 Diabetic Patients: A Case-Control Study

Subclinical hypothyroidism (SCH) is defined as an asymptomatic state characterized by normal serum levels of free thyroxine and elevated serum concentrations of thyrotropin (> 4.0 µU/ml). The association between SCH and type 2 diabetes has been well established. Proliferative diabetic retinopathy (PDR) that is characterized by neovascularization is a leading cause of visual loss in adults worldwide. However, whether SCH is related to PDR has not been studied. This study thus aimed to evaluate the relationship between SCH and PDR in type 2 diabetes. A total of 371 type 2 diabetic subjects were enrolled: 187 subjects with PDR and 184 subjects without diabetic retinopathy (with HbA1c above 6.5% and at least 10 years of diabetes duration). Subjects with PDR had higher blood pressure, higher serum levels of total cholesterol, low-density lipoprotein cholesterol and thyrotropin, and higher urinary albumin excretion rate. Of the 371 diabetics, 83 subjects (22.4%) were diagnosed as SCH (male 12.1% and female 29.9%). The prevalence of SCH in the PDR group (51/187, 27.3%) was higher than that in the subjects without diabetic retinopathy (32/184, 17.4%). Logistic regression analysis showed that after adjusting for compounding variables, SCH was independently related with PDR (p = 0.032, adjusted OR = 2.485). These results indicate that type 2 diabetic patients with PDR are at an increased risk of SCH. A routine screening for thyroid function may thus be considered advisable in PDR subjects. This may be helpful in investigating new strategies preventing or treating PDR in clinical practice.